The long non-coding RNAs (lncRNAs) and a subclass known as large intergenic non-coding RNAs (lincRNAs) comprise approximately 15,000 diverse transcripts in mammals that resemble mRNAs in structure, synthesis, and the chromatin character of their genes. Functions or phenotypes associated with particular lncRNAs are not known for the vast majority of identified lncRNAs. It is believed that some lncRNAs participate in transcriptional control as activators or repressors of transcription in animals; others may function post-translationally or by some other mechanism. Thus, the ability to manipulate lncRNAs may provide a tool for developing phenotypes of interest depending upon the identity and function of the lncRNA. There is a need in the art for methods and compositions for manipulating lncRNAs, and a need for generating phenotypes of non-human animals through lncRNA manipulation.